title: Positional cloning identifies zebrafish one-eyed pinhead as a permissive EGF-related ligand required during gastrulation.
abstract: The zebrafish one-eyed pinhead (oep) mutation disrupts embryonic development, resulting in cyclopia and defects in endoderm, prechordal plate, and ventral neuroectoderm formation. We report the molecular isolation of oep using a positional cloning approach. The oep gene encodes a novel EGF-related protein with similarity to the EGF-CFC proteins cripto, cryptic, and FRL-1. Wild-type oep protein contains a functional signal sequence and is membrane-associated. Following ubiquitous maternal and zygotic expression, highest levels of oep mRNA are found in the gastrula margin and in axial structures and forebrain. Widespread misexpression of both membrane-attached and secreted forms of oep rescues prechordal plate and forebrain development in mutant embryos but does not lead to the ectopic induction of these cell types in wild-type fish. These results establish an essential but permissive role for an EGF-related ligand during vertebrate gastrulation.
authors.affiliation: Developmental Genetics Program, Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University Medical Center, New York 10016, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: W S
authors.initials: WS
authors.lastname: Talbot
authors.forename: A F
authors.initials: AF
authors.lastname: Schier
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002462:Cell Membrane / Q000737:chemistry; D002490:Central Nervous System / Q000196:embryology; D003001:Cloning, Molecular / Q000379:methods*; D004707:Endoderm; D004815:Epidermal Growth Factor / Q000235:genetics; D005775:Gastrula / Q000737:chemistry / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D005796:Genes / Q000235:genetics; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D008024:Ligands; D008969:Molecular Sequence Data; D009154:Mutation; D021382:Protein Sorting Signals / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics* / Q000502:physiology; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins
chemical_list: D018398:Homeodomain Proteins; D008024:Ligands; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D014157:Transcription Factors; D029961:Zebrafish Proteins; C110484:tdgf1 protein, zebrafish; D004815:Epidermal Growth Factor